Endothelial preconditioning by transient oxidative stress reduces inflammatory responses of cultured endothelial cells to TNF-α

Brief episodes of ischemia can render an organ resistant to subsequent severe ischemia. This ‘ischemic preconditioning’ is ascribed to various mechanisms, including oxidative stress. We investigated whether preconditioning exists on an endothelial level. Human umbilical vein endothelial cells (HUVECs) were transiently confronted with oxidative stress (1 mM H2O2, 5 min). Adhesion molecules ICAM-1 and E-selectin and release of cytokines IL-6 and IL-8 to subsequent stimulation with TNF-α (2.5 ng/ml, 4 h) were measured (flow cytometry and immunoassay), as were nuclear translocation of the transcription factor NFkB (Western blotting, confocal microscopy) and redox status of HUVECs (quantification of glutathione by HPLC). TNF-α elevated IL-6 in the cell supernatant from 8.8 ± 1 to 41 ± 3 pg/ml and IL-8 from 0.5 ± 0.03 to 3 ± 0.2 ng/ml. ICAM-1 was increased threefold and E-selectin rose eightfold. Oxidative stress (decrease of glutathione by 50%) reduced post-TNF-α levels of IL-6 to 14 ± 3 and IL-8 to 1 ± 0.2; the rise of ICAM-1 was completely blocked and E-selectin was only doubled. The anti-inflammatory effects of preconditioning via oxidative stress were paralleled by reduction of the translocation of NFkB on stimulation with TNF-α, and antagonized by the intracellular radical scavenger N-acetylcysteine. ‘Anti-inflammatory preconditioning’ of endothelial cells by oxidative stress may account for the inhibitory effects of preconditioning on leukocyte adhesion in vivo

Community-Based User Experience: Evaluating the Usability of Health Insurance Information With Immigrant Patients

User experience (UX), a common practice in corporate settings, is new for many nonprofit organizations. This case study details a community-based research project between nonprofit staff at a community health center and UX professionals to improve the design and usability of a document designed to help immigrant patients sign up for health insurance. UX professionals may need to adapt and be flexible with their efforts, but can offer valuable skills to community partners. Research questions: (1) What are the information needs and barriers faced by immigrant populations signing up for health insurance? (2) How does a usability study, adapted to meet the needs of immigrant populations, inform the design of a supplemental guidebook about health insurance? (3) What are the challenges and opportunities when engaging in community-based UX research projects? Situating the case: Other community-based research projects in technical communication and UX point to the need for a clear conceptualization of participation, a strong partnership with nonprofits, and the need to develop meaningful and actionable insights. Furthermore, when conducting studies with immigrant populations, the role of the translator on the research team is crucial. Methodology: As a community-based research project focused on the collaborative generation of practical knowledge, we conducted a usability study with 12 participants in two language groups, Chinese and Vietnamese, to evaluate the design and usability of a guidebook designed to provide guidance about enrolling in a health insurance plan. Data were analyzed to identify usability concerns and used to inform a second iteration of the guidebook. About the case: Immigrant populations struggle to sign up for health insurance for a variety of reasons, including limited English and health insurance literacy. As a result, a nonprofit community health center developed a guidebook to support immigrant populations. Version 1 of this guidebook was evaluat- d in a usability study, with results showing that users struggled to correctly choose a plan, determine their eligibility, and interpret abstract examples. As a result, Version 2 was designed to support the in-person experience, reduce visual complexity, and support patients\u27 key questions. Conclusions: Community-based UX collaborations can amplify the expertise of UX and nonprofit professionals. However, UX methods may need to be adapted in community-based projects to better incorporate local knowledge and needs

A previously unidentified Chorioptes species infesting outer ear canals of moose (Alces alces): characterization of the mite and the pathology of infestation

<p>Abstract</p> <p>Background</p> <p>During the past decade, <it>Chorioptes </it>mites occupying the outer ear canals have been a common finding at routine necropsies of moose (<it>Alces alces</it>) in Sweden, but neither the taxonomy of the mites nor lesions from the infestation have been investigated. In this study, the mites are characterized by morphological and molecular techniques, and the histopathology of the skin of the outer ear canal is described.</p> <p>Methods</p> <p>External auditory meatuses from 53 necropsied moose were examined for the presence of <it>Chorioptes</it>, and samples from outer ear canals were taken for histopathological and microbiological examination. A proportion of the mites from each moose was identified to species. The DNA was extracted from mites from three moose, and their ITS-2 sequences were determined; these sequences were compared phylogenetically to sequences from other <it>Chorioptes </it>taxa.</p> <p>Results</p> <p><it>Chorioptes </it>mites were found in 43 (81%) of the 53 moose. The mites had morphological and genetic characteristics distinct from those of <it>C. texanus </it>and <it>C. bovis</it>, the two species generally accepted within the genus. Morphology also did not argue for a diagnosis as <it>C. crewei</it>, <it>C. mydaus </it>or <it>C. panda</it>. On histopathology, lesions were characterized by a hyperplastic perivascular to interstitial dermatitis with epidermal hyperkeratosis and crust formation. Dermal inflammatory infiltrates were composed of mixed T- and B-lymphocytes, plasma cells and macrophages, whereas eosinophils were notably uncommon. <it>Staphylococcus aureus </it>was grown from the infested epidermis of five of 14 examined moose.</p> <p>Conclusion</p> <p><it>Chorioptes </it>mite infestation was frequently detected in the outer ear canals of moose in Sweden. The mites were evidently pathogenic, being associated with inflammatory lesions of the external auditory meatus. Our studies indicate infestations with a previously undescribed <it>Chorioptes </it>species.</p

Preparation and control of a cavity-field state through atom-driven field interaction: towards long-lived mesoscopic states

The preparation of mesoscopic states of the radiation and matter fields through atom-field interactions has been achieved in recent years and employed for a range of striking applications in quantum optics. Here we present a technique for the preparation and control of a cavity mode which, besides interacting with a two-level atom, is simultaneously submitted to linear and parametric amplification processes. The role of the amplification-controlling fields in the achievement of real mesoscopic states, is to produce highly-squeezed field states and, consequently, to increase both: i) the distance in phase space between the components of the prepared superpositions and ii) the mean photon number of such superpositions. When submitting the squeezed superposition states to the action of similarly squeezed reservoirs, we demonstrate that under specific conditions the decoherence time of the states becomes independent of both the distance in phase space between their components and their mean photon number. An explanation is presented to support this remarkable result, together with a discussion on the experimental implementation of our proposal. We also show how to produce number states with fidelities higher than those derived as circular states

Investigation of catalysis by bacterial RNase P via LNA and other modifications at the scissile phosphodiester

We analyzed cleavage of precursor tRNAs with an LNA, 2′-OCH3, 2′-H or 2′-F modification at the canonical (c0) site by bacterial RNase P. We infer that the major function of the 2′-substituent at nt −1 during substrate ground state binding is to accept an H-bond. Cleavage of the LNA substrate at the c0 site by Escherichia coli RNase P RNA demonstrated that the transition state for cleavage can in principle be achieved with a locked C3′ -endo ribose and without the H-bond donor function of the 2′-substituent. LNA and 2′-OCH3 suppressed processing at the major aberrant m−1 site; instead, the m+1 (nt +1/+2) site was utilized. For the LNA variant, parallel pathways leading to cleavage at the c0 and m+1 sites had different pH profiles, with a higher Mg2+ requirement for c0 versus m+1 cleavage. The strong catalytic defect for LNA and 2′-OCH3 supports a model where the extra methylene (LNA) or methyl group (2′-OCH3) causes a steric interference with a nearby bound catalytic Mg2+ during its recoordination on the way to the transition state for cleavage. The presence of the protein cofactor suppressed the ground state binding defects, but not the catalytic defects

Molecular epidemiology of camel trypanosomiasis based on ITS1 rDNA and RoTat 1.2 VSG gene in the Sudan

<p>Abstract</p> <p>Background</p> <p>Internal transcribed spacer one (ITS1) of the ribosomal DNA is known to be a suitable target for PCR-based detection of trypanosomes. The analysis of this region provides a multi-species-specific diagnosis by a single PCR. Using ITS1 primer-based PCR, a cross sectional study was carried out in the period from September to November 2009 on samples collected from 687 camels from geographically distinct zones in the Sudan to detect all possible African trypanosomes, which can infect camels.</p> <p>Results</p> <p>The results showed that all PCR-positive camels were infected with a single parasite species; <it>Trypanosoma evansi</it>. The highest prevalence, 57.1% (117/205), was observed in the Butana plains of mid-Eastern Sudan and the lowest, 6.0% (4/67), was in the Umshadeeda eastern part of White Nile State. In another experiment, the RoTat 1.2 gene encoding the variable surface glycoprotein (VSG) of <it>T. evansi </it>was analyzed for its presence or absence by a polymerase chain reaction (PCR) using <it>T. evansi </it>species-specific primers. The study showed that the RoTat 1.2 VSG gene was absent in thirteen out of thirty <it>T. evansi</it>-positive samples.</p> <p>Conclusions</p> <p>It is concluded that camel trypanosomiasis in Sudan is apparently caused by a single parasite species <it>T. evansi </it>and there were no other typanosomes species detected. In addition, the disease is highly prevalent in the country, which strengthens the need to change control policies and institute measures that help prevent the spread of the parasite. To our knowledge, this is the first molecular diagnosis report, which gives a picture of camel trypanosomiasis covering large geographical areas in Sudan.</p

P-value based visualization of codon usage data

Two important and not yet solved problems in bacterial genome research are the identification of horizontally transferred genes and the prediction of gene expression levels. Both problems can be addressed by multivariate analysis of codon usage data. In particular dimensionality reduction methods for visualization of multivariate data have shown to be effective tools for codon usage analysis. We here propose a multidimensional scaling approach using a novel similarity measure for codon usage tables. Our probabilistic similarity measure is based on P-values derived from the well-known chi-square test for comparison of two distributions. Experimental results on four microbial genomes indicate that the new method is well-suited for the analysis of horizontal gene transfer and translational selection. As compared with the widely-used correspondence analysis, our method did not suffer from outlier sensitivity and showed a better clustering of putative alien genes in most cases

Longitudinal evaluation the pulmonary function of the pre and postoperative periods in the coronary artery bypass graft surgery of patients treated with a physiotherapy protocol

<p>Abstract</p> <p>Background</p> <p>The treatment of coronary artery disease (CAD) seeks to reduce or prevent its complications and decrease morbidity and mortality. For certain subgroups of patients, coronary artery bypass graft surgery (CABG) may accomplish these goals. The objective of this study was to assess the pulmonary function in the CABG postoperative period of patients treated with a physiotherapy protocol.</p> <p>Methods</p> <p>Forty-two volunteers with an average age of 63 ± 2 years were included and separated into three groups: healthy volunteers (n = 09), patients with CAD (n = 9) and patients who underwent CABG (n = 20). Patients from the CABG group received preoperative and postoperative evaluations on days 3, 6, 15 and 30. Patients from the CAD group had evaluations on days 1 and 30 of the study, and the healthy volunteers were evaluated on day 1. Pulmonary function was evaluated by measuring forced vital capacity (FVC), maximum expiratory pressure (MEP) and Maximum inspiratory pressure (MIP).</p> <p>Results</p> <p>After CABG, there was a significant decrease in pulmonary function (p < 0.05), which was the worst on postoperative day 3 and returned to the preoperative baseline on postoperative day 30.</p> <p>Conclusion</p> <p>Pulmonary function decreased after CABG. Pulmonary function was the worst on postoperative day 3 and began to improve on postoperative day 15. Pulmonary function returned to the preoperative baseline on postoperative day 30.</p

DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential.

Single-stranded guanine-rich DNA sequences can fold into four-stranded DNA structures called G-quadruplexes (G4s) that arise from the self-stacking of two or more guanine quartets. There has been considerable recent progress in the detection and mapping of G4 structures in the human genome and in biologically relevant contexts. These advancements, many of which align with predictions made previously in computational studies, provide important new insights into the functions of G4 structures in, for example, the regulation of transcription and genome stability, and uncover their potential relevance for cancer therapy.The Balasubramanian laboratory is core-funded by Cancer Research UK (C14303/A17197) and further supported by a Cancer Research UK programme grant (C9681/A18618). S.B. is a Wellcome Trust Senior Investigator (099232/Z/12/Z)